Development of Heck and Desaturation Reactions Involving Novel Hybrid Palladium-Radical Intermediates

The first part of the thesis focuses on the development of the first endo-selective Pd-catalyzed Heck reaction of iodomethylsilyl ethers of phenols and alkenols leading to valuable allylic silyloxycylces. Mechanistic studies revealed that the transformation operates via a novel hybrid Pd-radical process. Also, it was found that the silicon atom is crucial for the observed endo selectivity, and it also enables post-modification of the reaction products. The obtained allylic silyloxycylces were efficiently oxidized to form Z-1,5-alkenols, which highlights our protocol as a useful tool for a formal Z-hydroxymethylation of a broad range of alkenols. The second part of the thesis discloses the development of an unprecedented visible-light induced Pd-catalyzed remote desaturation of aliphatic alcohols. Our strategy involves the development of silicon tethers that allow for auxiliary-controlled α-/β-, β-/γ-, γ-/δ-, and δ-/ε- desaturation of alcohols leading to valuable alkenol building blocks. This work involves a new mechanistic approach for remote C–H functionalization involving hybrid Pd-radical intermediates, which possess both radical and Pd character that enables a radical hydrogen atom transfer (HAT) reaction and a Pd-involved β-hydride elimination event to occur. The latter feature of the mechanism results in desaturation of alcohols with superior degrees of regioselectivity compared to the state-of-the-art desaturation methods

Endo-Selective Pd-Catalyzed Silyl Methyl Heck Reaction

A palladium (Pd)-catalyzed endo-selective Heck reaction of iodomethylsilyl ethers of phenols and aliphatic alkenols has been developed. Mechanistic studies reveal that this silyl methyl Heck reaction operates via a hybrid Pd-radical process and that the silicon atom is crucial for the observed endo selectivity. The obtained allylic silyloxycycles were further oxidized into (<i>Z</i>)-alkenyldiols

Photoinduced Formation of Hybrid Aryl Pd-Radical Species Capable of 1,5-HAT: Selective Catalytic Oxidation of Silyl Ethers into Silyl Enol Ethers

A direct visible light-induced generation of a hybrid aryl Pd-radical species from aryl iodide and Pd(0) is reported to enable an unprecedented (for hybrid Pd-radical species) hydrogen atom-transfer event. This approach allowed for efficient desaturation of readily available silyl ethers into synthetically valuable silyl enols. Moreover, this oxidation reaction proceeds at room temperature without the aid of exogenous photosensitizers or oxidants

General, Auxiliary-Enabled Photoinduced Pd-Catalyzed Remote Desaturation of Aliphatic Alcohols

A general, efficient, and site-selective visible light-induced Pd-catalyzed remote desaturation of aliphatic alcohols into valuable allylic, homoallylic, and bis-homoallylic alcohols has been developed. This transformation operates via a hybrid Pd-radical mechanism, which synergistically combines the favorable features of radical approaches, such as a facile remote C–H HAT step, with that of transition-metal-catalyzed chemistry (selective β-hydrogen elimination step). This allows achieving superior degrees of regioselectivity and yields in the desaturation of alcohols compared to those obtained by the state-of-the-art desaturation methods. The HAT at unactivated C­(sp³)–H sites is enabled by the easily installable/removable Si-auxiliaries. Formation of the key hybrid alkyl Pd-radical intermediates is efficiently induced by visible light from alkyl iodides and Pd(0) complexes. Notably, this method requires no exogenous photosensitizers or external oxidants